Multi-modal data integration platform combining clinical and preclinical models of post subarachnoid hemorrhage epilepsy.

Subarachnoid hemorrhage (SAH) is a devastating neurological injury that can lead to many downstream complications including epilepsy. Predicting who will get epilepsy in order to find ways to prevent it as well as stratify patients for future interventions is a major challenge given the large number of variables not only related to the injury itself, but also to what happens after the injury. Extensive multimodal data are generated during the process of SAH patient care. In parallel, preclinical models are under development that attempt to imitate the variables observed in patients. Computational tools that consider all variables from both human data and animal models are lacking and demand an integrated, time-dependent platform where researchers can aggregate, store, visualize, analyze, and share the extensive integrated multimodal information. We developed a multi-tier web-based application that is secure, extensible, and adaptable to all available data modalities using flask micro-web framework, python, and PostgreSQL database. The system supports data visualization, data sharing and downloading for offline processing. The system is currently hosted inside the institutional private network and holds [Formula: see text] of data from 164 patients and 71 rodents. Clinical Relevance-Our platform supports clinical and preclinical data management. It allows users to comprehensively visualize patient data and perform visual analytics. These utilities can improve research and clinical practice for subarachnoid hemorrhage and other brain injuries.

Systemic Immune-Inflammation Index Predicts Delayed Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral vasospasm is a feared complication of aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: To investigate the relationship of systemic inflammation, measured using the systemic immune-inflammation (SII) index, with delayed angiographic or sonographic vasospasm. We hypothesize that early elevations in SII index serve as an independent predictor of vasospasm. METHODS: We retrospectively reviewed the medical records of 289 SAH patients for angiographic or sonographic evidence of delayed cerebral vasospasm. SII index [(neutrophils × platelets/lymphocytes)/1000] was calculated from laboratory data at admission and dichotomized based on whether or not the patient developed vasospasm. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to determine the ability of SII index to predict the development of vasospasm. RESULTS: A total of 246 patients were included in our study, of which 166 (67.5%) developed angiographic or sonographic evidence of cerebral vasospasm. Admission SII index was elevated for SAH in patients with vasospasm compared to those without (P < .001). In univariate logistic regression, leukocytes, neutrophils, lymphocytes, neutrophil-lymphocyte ratio (NLR), and SII index were associated with vasospasm. After adjustment for age, aneurysm location, diabetes mellitus, hyperlipidemia, and modified Fisher scale, SII index remained an independent predictor of vasospasm (odds ratio 1.386, P = .003). ROC analysis revealed that SII index accurately distinguished between patients who develop vasospasm vs those who do not (area under the curve = 0.767, P < .001). CONCLUSION: Early elevation in SII index can independently predict the development of delayed cerebral vasospasm in aneurysmal SAH.

Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

An electrodiagnostic grading system for ulnar neuropathy at the elbow.

INTRODUCTION: Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy. Our goal was to create and analyze a grading system for UNE electrodiagnostic severity. METHODS: We retrospectively analyzed EMG reports with UNE. We then classified 112 limbs as having mild, moderate, or severe grade UNE based on electrodiagnostic findings. The association between presenting symptoms and signs, EMG findings, treatment type, and electrodiagnostic grade was statistically analyzed. RESULTS: Seventeen limbs (15.2%) had mild, 80 (71.4%) had moderate, and 15 (13.4%) had severe UNE. Symptoms (P = .016), exam findings (P < .001), and treatment type (P = .043) were significantly associated with electrodiagnostic grade. DISCUSSION: Our UNE grading system was significantly related to symptoms, physical exam, and treatment selection and may be useful to measure electrodiagnostic severity.

Enhancing epilepsy self-management and quality of life for adults with epilepsy with varying social and educational backgrounds using PAUSE to Learn Your Epilepsy.

PURPOSE: People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QOL), and personal impact of epilepsy in adults with epilepsy. METHODS: Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Epilepsy.com. Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8-12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2). Multiple linear regression was used to assess within-subject significant changes in outcome measures between these time points. RESULTS: The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in the majority of SM measures from T1 to T2. CONCLUSION: This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QOL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE.

Optimized Hemodynamic Assessment to Predict Stroke Risk in Vertebrobasilar Disease: Analysis From the VERiTAS Study.

Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent vertebrobasilar stroke risk. We sought to compare predictive models using thresholds for posterior circulation vessel flows standardized to age and vascular anatomy to optimize risk prediction. Methods and Results VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis/occlusion in vertebral and/or basilar arteries. Quantitative magnetic resonance angiography measured large-vessel vertebrobasilar territory flow, and patients were designated as low or normal flow based on a prespecified empiric algorithm considering distal territory regional flow and collateral capacity. For the present study, post hoc analysis was performed to generate additional predictive models using age-specific normalized flow measurements. Sensitivity, specificity, and time-to-event analyses were compared between the algorithms. The original prespecified algorithm had 50% sensitivity and 79% specificity for future stroke risk prediction; using a predictive model based on age-normalized flows in the basilar and posterior cerebral arteries, standardized to vascular anatomy, optimized flow status thresholds were identified. The optimized algorithm maintained sensitivity and increased specificity to 84%, while demonstrating a larger and more significant hazard ratio for stroke on time-to-event analysis. Conclusions These results indicate that flow remains a strong predictor of stroke across different predictive models, and suggest that prediction of future stroke risk can be optimized by use of vascular anatomy and age-specific normalized flows.

Infarct Patterns in Patients with Atherosclerotic Vertebrobasilar Disease in Relation to Hemodynamics.

INTRODUCTION: Distal territory blood flow is independently associated with subsequent strokes in symptomatic vertebrobasilar atherosclerotic disease. We aimed to assess infarct patterns in relation to hemodynamic status in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. METHODS: Distal territory blood flow was measured using quantitative magnetic resonance angiography (MRA) in 72 patients with symptomatic atherosclerotic vertebrobasilar disease, and then dichotomized into normal (n = 54) and low (n = 18) flow. Patients were followed longitudinally on standard medical management. Two observers blinded to flow status independently reviewed the imaging performed at the time of subsequent strokes, in order to adjudicate the likely mechanism based on infarct patterns. The frequency of stroke mechanisms was qualitatively compared based on flow status. RESULTS: During a median follow-up period of 23 months, 10/72 patients had a subsequent stroke; 5 of these had low distal flow. Infarct patterns were adjudicated to be consistent with hemodynamic (n = 2), embolic (n = 4), and junctional plaque/perforator (n = 4) infarcts. Hemodynamic infarcts were seen in 40% (2/5) low-flow patients, in comparison to 0% (0/5) normal-flow patients. CONCLUSION: In contrast to normal-flow patients, those with low distal flow seem to be uniquely susceptible to hemodynamic infarctions, although other patterns of infarction can also be seen in these hemodynamically impaired patients.

Self-management for adults with epilepsy: Aggregate Managing Epilepsy Well Network findings on depressive symptoms.

OBJECTIVE: To assess depressive symptom outcomes in a pooled sample of epilepsy self-management randomized controlled trials (RCTs) from the Managing Epilepsy Well (MEW) Network integrated research database (MEW DB). METHODS: Five prospective RCTs involving 453 adults with epilepsy compared self-management intervention (n = 232) versus treatment as usual or wait-list control outcomes (n = 221). Depression was assessed with the nine-item Patient Health Questionnaire. Other variables included age, gender, race, ethnicity, education, income, marital status, seizure frequency, and quality of life. Follow-up assessments were collapsed into a visit 2 and a visit 3; these were conducted postbaseline. RESULTS: Mean age was 43.5 years (SD = 12.6), nearly two-thirds were women, and nearly one-third were African American. Baseline sample characteristics were mostly similar in the self-management intervention group versus controls. At follow-up, the self-management group had a significantly greater reduction in depression compared to controls at visit 2 (P < .0001) and visit 3 (P = .0002). Quality of life also significantly improved in the self-management group at visit 2 (P = .001) and visit 3 (P = .005). SIGNIFICANCE: Aggregate MEW DB analysis of five RCTs found depressive symptom severity and quality of life significantly improved in individuals randomized to self-management intervention versus controls. Evidence-based epilepsy self-management programs should be made more broadly available in neurology practices.

Self-management skills and behaviors, self-efficacy, and quality of life in people with epilepsy from underserved populations.

PURPOSE: People with epilepsy (PWE) from underserved populations face significant barriers to epilepsy management and therefore may lack knowledge about epilepsy and self-management (SM) of epilepsy. This paper evaluates SM practices, self-efficacy, outcome expectancy, quality of life, and personal impact of epilepsy in PWE from underserved populations as compared with all PWE. METHODS: Recruitment for the Managing Epilepsy Well (MEW) Network PAUSE to Learn Your Epilepsy study occurred from October 2015 to March 2019. Participants were assessed at baseline; after SM education intervention; and 6-, 9-, and 15-month postbaseline assessment. Baseline data from 112 PWE were analyzed for this report. RESULTS: Study population was diverse: 63% were women, 47.3% were non-Hispanic black, 24.1% were Hispanic, and 57.4% had public healthcare coverage. Participants on average had epilepsy for 14 years, and 49.1% reported at least one seizure within the past month, but only 27% reported having used a seizure diary or calendar for seizure tracking. Self-management practices & behaviors were significantly lower among PWE from underserved populations than all PWE, though self-efficacy among PWE from underserved populations was significantly higher. CONCLUSION: This study identifies the unique epilepsy SM needs of PWE from underserved populations. We discuss the need for a personalized approach for developing SM skills and behaviors among these PWE.

Nickel-Catalyzed C(2)-H Arylation of Indoles with Aryl Chlorides under Neat Conditions.

Nickel-catalyzed regioselective C(2)-H arylation of indoles and pyrroles with aryl chlorides is achieved under neat conditions. This method allows the efficient coupling of diverse aryl chlorides employing a user-friendly and inexpensive Ni(OAc)2/dppf catalyst system at 80 °C. Numerous functionalities, such as halides, alkyl ether, fluoro-alkyl ether, and thioether, and substituted amines, including heteroarenes like benzothiazolyl, pyrrolyl, indolyl, and carbazolyl, are well tolerated under the reaction conditions. The preliminary mechanistic study highlights a single-electron transfer (SET) pathway for the arylation reaction.

Nickel-catalyzed C-H alkylation of indoles with unactivated alkyl chlorides: evidence of a Ni(i)/Ni(iii) pathway.

A mild and efficient nickel-catalyzed method for the coupling of unactivated primary and secondary alkyl chlorides with the C-H bond of indoles and pyrroles is described which demonstrates a high level of chemo and regioselectivity. The reaction tolerates numerous functionalities, such as halide, alkenyl, alkynyl, ether, thioether, furanyl, pyrrolyl, indolyl and carbazolyl groups including acyclic and cyclic alkyls under the reaction conditions. Mechanistic investigation highlights that the alkylation proceeds through a single-electron transfer (SET) process with Ni(i)-species being the active catalyst. Overall, the alkylation follows a Ni(i)/Ni(iii) pathway involving the rate-influencing two-step single-electron oxidative addition of alkyl chlorides.

Hypoperfusion Symptoms Poorly Predict Hemodynamic Compromise and Stroke Risk in Vertebrobasilar Disease.

Background and Purpose- Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke). Methods- VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using quantitative magnetic resonance angiography, and patients were designated as low, borderline, or normal flow based on distal territory regional flow, incorporating collateral capacity. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal versus borderline/low) and also examined as a predictor of subsequent stroke risk. Results- Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial quantitative magnetic resonance angiography designation, 43 subjects were designated as normal flow versus 23 subjects designated as low flow (n=16) or borderline flow (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom ( P=0.99, Fisher exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared with flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome ( P=0.87, log-rank test). Conclusions- These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise as assessed by quantitative magnetic resonance angiography and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00590980.

Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association.

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.

A carpal tunnel grading system including combined sensory index-diagnosed mild cases: Relation to presenting features and outcomes.

INTRODUCTION: Prior studies have demonstrated superiority of the combined sensory index (CSI) algorithm in diagnosing mild carpal tunnel syndrome (CTS) and have compared presenting symptoms to CTS grade. However, CTS symptoms, signs, and outcomes, including CSI-diagnosed cases, have not been compared with CTS grade. METHODS: We retrospectively studied 294 CTS hands from 2010 to 2013; stratified them into mild, moderate, and severe grades; and analyzed the association between CTS grade and presenting symptoms/signs and outcomes. RESULTS: Sensorimotor symptoms (P = 0.017) and signs (P < 0.001) were significantly associated with CTS grade. Regardless of CTS grade, 94% of hands improved with surgery compared with 42% with conservative treatment (P < 0.001). Even in mild CTS, 100% improved with surgery vs. 33% with conservative management (P = 0.011). DISCUSSION: These results corroborate prior studies that compared symptoms to CTS grade and suggest that more objective signs associate even better. CTS grades associate with outcomes, but additional studies are required. Muscle Nerve 57: 45-48, 2018.

The Managing Epilepsy Well Network:: Advancing Epilepsy Self-Management.

Epilepsy, a complex spectrum of disorders, affects about 2.9 million people in the U.S. Similar to other chronic disorders, people with epilepsy face challenges related to management of the disorder, its treatment, co-occurring depression, disability, social disadvantages, and stigma. Two national conferences on public health and epilepsy (1997, 2003) and a 2012 IOM report on the public health dimensions of epilepsy highlighted important knowledge gaps and emphasized the need for evidence-based, scalable epilepsy self-management programs. The Centers for Disease Control and Prevention translated recommendations on self-management research and dissemination into an applied research program through the Prevention Research Centers Managing Epilepsy Well (MEW) Network. MEW Network objectives are to advance epilepsy self-management research by developing effective interventions that can be broadly disseminated for use in people's homes, healthcare providers' offices, or in community settings. The aim of this report is to provide an update on the MEW Network research pipeline, which spans efficacy, effectiveness, and dissemination. Many of the interventions use e-health strategies to eliminate barriers to care (e.g., lack of transportation, functional limitations, and stigma). Strengths of this mature research network are the culture of collaboration, community-based partnerships, e-health methods, and its portfolio of prevention activities, which range from efficacy studies engaging hard-to-reach groups, to initiatives focused on provider training and knowledge translation. The MEW Network works with organizations across the country to expand its capacity, help leverage funding and other resources, and enhance the development, dissemination, and sustainability of MEW Network programs and tools. Guided by national initiatives targeting chronic disease or epilepsy burden since 2007, the MEW Network has been responsible for more than 43 scientific journal articles, two study reports, seven book chapters, and 62 presentations and posters. To date, two programs have been adopted and disseminated by the national Epilepsy Foundation, state Epilepsy Foundation affiliates, and other stakeholders. Recent expansion of the MEW Network membership will help to extend future reach and public health impact.

Higher Stroke Risk with Lower Blood Pressure in Hemodynamic Vertebrobasilar Disease: Analysis from the VERiTAS Study.

BACKGROUND: Despite concerns regarding hypoperfusion in patients with large-artery occlusive disease, strict blood pressure (BP) control has become adopted as a safe strategy for risk reduction of stroke. We examined the relationship between BP control, blood flow, and risk of subsequent stroke in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. METHODS: The VERiTAS study enrolled patients with recent vertebrobasilar (VB) transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral or basilar arteries. Hemodynamic status was designated as low or normal based on quantitative magnetic resonance angiography. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. Mean BP during follow-up (<140/90 versus ≥140/90 mm Hg) and flow status were examined relative to subsequent stroke risk using Cox proportional hazards analysis. RESULTS: The 72 subjects had an average of 3.8 ± 1.2 BP recordings over 20 ± 8 months of follow-up; 39 (54%) had mean BP of<140/90 mm Hg. The BP groups were largely comparable for baseline demographics, risk factors, and stenosis severity. Comparing subgroups stratified by BP and hemodynamic status, we found that patients with both low flow and BP <140/90 mm Hg (n = 10) had the highest risk of subsequent stroke, with hazard ratio of 4.5 (confidence interval 1.3-16.0, P = .02), compared with the other subgroups combined. CONCLUSIONS: Among a subgroup of patients with VB disease and low flow, strict BP control (BP <140/90) may increase the risk of subsequent stroke.